The papillomaviruses are widespread in nature and are generally associated with benign epithelial and fibroepithelial lesions in their natural hosts, including humans. Although there is no system to study papillomavirus infection in tissue culture, bovine papillomavirus type 1 (BPV-l) has provided an excellent model system for a systematic study of the molecular biology of the papillomaviruses. BPV-l readily transforms a variety of rodent cells in tissue culture. In these transformed cells, viral genes are expressed which are responsible for the transformed state as well as for other functions such as viral DNA replication and episomal maintenance of the viral genome. Our studies have been designed to focus on the molecular biology of the BPV-l/host cell interaction. Critical to the investigation of this interaction is the identification of the promoters responsible for the expression of the various viral gene products and a characterization of the elements which regulate expression from those promoters. We have previously described the important role the viral E2 gene products play in viral gene expression and have now shown that many of the BPV-1 promoters are regulated by these products, including the promoters responsible for expression of the E2 gene products themselves. Similarly, we have begun to identify cellular factors which also play a role in regulating viral gene expression and have found that the ubiquitous transcription factor SP1 plays in important role. Equally important as transcriptional control in understanding BPV/host cell interactions are the mechanisms controlling viral replication, particularly as preliminary localization of replicating cis elements map very near major transcriptional elements. Characterization of the elements involved in viral replication is therefore also underway.